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HPMR

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hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) OKDB#: 4035
 Symbols: H6PD Species: human
 Synonyms: GDH, G6PDH,GDH, G6PDH, MGC87643, DKFZp686A01246,GDH/6PGL ENDOPLASMIC BIFUNCTIONAL PROTEIN|HEXOSE-6-PHOSPHATE DEHYDROGENASE PRECURSOR|GLUCOSE-6-PHOSPHATE DEHYDROGENASE, SALIVARY|G6PD, H FORM, G6PDH|GLUCOSE 1-DEHYDROGENASE|GLUCOSE DEHYDROGENASE, GDH  Locus: 1p36 in Homo sapiens


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General Comment NCBI Summary: There are 2 forms of glucose-6-phosphate dehydrogenase. G form is X-linked and H form, encoded by this gene, is autosomally linked. This H form shows activity with other hexose-6-phosphates, especially galactose-6-phosphate, whereas the G form is specific for glucose-6-phosphate. Both forms are present in most tissues, but H form is not found in red cells. [provided by RefSeq, Jul 2008]
General function Enzyme
Comment
Cellular localization Cytoplasmic
Comment
Ovarian function Early embryo development
Comment Meiotic progression, mitochondrial features and fertilisation characteristics of porcine oocytes with different G6PDH activities. Egerszegi I et al. The aim of the present study was to investigate the developmental competence, mitochondrial characteristics and chromatin status of immature follicular porcine oocytes selected for their glucose-6-phosphate dehydrogenase (G6PDH) activity by brilliant cresyl blue (BCB) staining. In Experiment 1, the oocyte parameters were determined in parallel right after BCB staining (T(0)), after 22 h of in vitro maturation (IVM) (T(22)) and after 44 h of IVM (T(44)) (n = 496). BCB-stained oocytes (BCB+) at T(0) were characterised by fibrillated chromatin filaments in their germinal vesicles (GV) and diakinesis stages whereas unstained (BCB-) oocytes at T(0) contained in their GV mainly condensed stages of chromatin (P < 0.05). After 22 h of IVM BCB+ oocytes showed a prominent chromatin configuration of metaphase I and after 44 h the majority developed a M II nuclear configuration in contrast to the BCB- group (P < 0.0001). Differences were also observed between the two oocyte populations in their mitochondrial activity (P < 0.05). At the beginning of IVM BCB+ oocytes were characterised by high mitochondrial activity in their cytoplasm. The BCB+ oocytes showed clear visible homogenous distributions of mitochondria (P < 0.005) and contained more aggregated clusters of mitochondria in contrast to BCB- oocytes (P < 0.005). In Experiment 2, 318 oocytes were tested for their G6PDH activity and introduced to IVM and IVF. Only oocytes from the BCB+ group, which were matured after 44 h up to the stage of M II (81.6%) were fertilised (17.4%), penetrated (46%) or activated (15.6%) after IVF. These results indicate a relationship between the G6PDH activity of porcine oocytes before IVM and their subsequent nuclear development, mitochondrial activity and aggregation.
Expression regulated by
Comment
Ovarian localization
Comment Immunohistochemical Demonstration of the Mineralocorticoid Receptor, 11{beta}-Hydroxysteroid Dehydrogenase 1 and 2, and Hexose-6-Phosphate Dehydrogenase in Rat Ovary. Gomez-Sanchez EP et al. An immunohistochemical (IHC) survey using several monoclonal antibodies against different portions of the rat mineralocorticoid receptor (MR) molecule demonstrated significant specific MR immunoreactivity in the ovary, prompting further study of the localization of MR and determinants of extrinsic MR ligand specificity, 11ss-hydroxysteroid dehydrogenase 1 and 2 (11ss-HSD), and hexose-6-phosphate dehydrogenase (H6PDH). MR expression (real-time RT-PCR and western blot) did not differ significantly in whole rat ovaries at early diestrus, late diestrus, estrus, and a few hours after ovulation. MR immunostaining was most intense in corporal lutea cells, light to moderate in oocytes and granulosa cells, and least intense in theca cells. Light immunoreactivity for 11ss-HSD 2 occurred in most cells with some mural granulosa cells of mature follicles staining more strongly. The distribution of immunoreactivity for 11ss-HSD 1 and H6PDH required to generate NADPH, the co-factor required for reductase activity of 11ss-HSD 1, was similar, with the most intense staining in the cytoplasm of corporal lutea and theca cells and light or no staining in the granulosa and oocytes. MR function in the ovary is yet unclear, but distinct patterns of distribution of the 11ss-HSD 2, 11ss-HSD1 and H6PDH suggest that the ligand for MR activation in different cells of the ovary may be differentially regulated.
Follicle stages
Comment
Phenotypes PCO (polycystic ovarian syndrome)
Mutations 1 mutations

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: The R453Q and D151A polymorphisms of Hexose-6-Phosphate Dehydrogenase Gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity. Martnez-Garca MA et al. Hexose-6-phosphate dehydrogenase (H6PDH) influences 11-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (?(2)=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (?(2)=3.95, P=0.047), specially within the PCOS subgroup (?(2)=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R(2)=0.490; ?(2)=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10-1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27-0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism.

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created: March 11, 2009, 11:34 a.m. by: hsueh   email:
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last update: Feb. 8, 2012, 12:05 p.m. by: hsueh    email:



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